The anti-tuberculosis BCG vaccine was conceived and developed between 1905 and 1921 at Pasteur Institutes in France. Between 1921 and A. Calmette’s death in 1933, the vaccine went through a first period of national and international production and distribution for its use in humans. In France these activities were exclusively carried out by Calmette and his collaborators at the Pasteur Institute in Paris. Initially improvised production in a small room in the cellar gave way in 1931 to the construction of (...) the spacious and magnificent ‘New laboratories for research on tuberculosis and the preparation of the BCG’ within the premises of the Pasteur Institute. Presentation and image-building of the vaccine in France insisted on the fact that the BCG was not a commercial specialty but distributed free of charge. The technical monopoly of its production nevertheless lay with the Paris Pasteur Institute and standardization of scientific proof of safety, efficacy and stability was dominated by that Institute in France. In contrast, the international production and distribution of the vaccine was entrusted and transferred, free of charge, to trustworthy laboratories outside France. Multiplication of producers and users led to an increased need for standardization. For this process the analysis distinguishes between the standardization of scientific proof concerning safety, efficacy and stability of the vaccine and standardization of its medical uses. Whereas standardization was rather successful in the inter-war period in France, the international efforts remained rather unsuccessful. Only after world war II under Scandinavian leadership and in the context of mass vaccination programs supported by the WHO and UNICEF was the international standardization effectively implemented and succeeded at least to some extend. (shrink)

ArgumentUsing the example of the anti-tuberculosis vaccine BCG during the 1920s and 1930s, this article asks how a labile laboratory-modified bacteria was transformed into a genuine standard vaccine packaged and commercialized as a pharmaceutical product. At the center of the analysis lies the notion of standardization inquiring why and how a local laboratory process with standard operating procedures (SOPs) reached its limits and was transformed when the product faced international distribution. Moving from Paul Ehrlich's initial technological notion ofWertbestimmungreferring to a (...) practice physiologically testing the effects of ill-defined antitoxins, the concept of standardization is extended to pharmaceutical and economical meanings implying quality control for biological therapeutic agents produced by a variety of industrial entrepreneurs. Following the request for product uniformity, two ways to maintain levels of compatibility and commonality are depicted opposing SOPs and end-product control. Furthermore, standardization is understood as a spiral, never ending process where progressive transformation of the vaccine in its production and medical uses periodically recreated the necessity of standardization. Developments analyzed are thus understood as a stabilization process aligning laboratory settings, products, and practices with medical theories and practices through technical, bureaucratic, and organizational systems. A paradox of the analysis is that standardization as a historical phenomenon and moment in the history of drug development was initially linked to a problem of under-determination of what was to be standardized and to a knowledge gap before it could become a central concept for quality control. (shrink)